Genetic Testing

Genetic testing is part of routine prenatal care and ideally occurs before conception. The scope of the desired by a woman genetic testing depends on how important factors such as the probability of a fetal abnormality in risk factors and the results of a previous study, the probability of a complication of invasive fetal examination The importance of knowing the test results (eg. as would the pregnancy be terminated when an abnormality has been diagnosed, would the lack of knowledge of the result afraid result) Therefore, to make the decision individually, and recommendations can not be generalized to all women mostly, even if they have a similar risk , A targeted history is part of the investigation. The history is like a family tree together (symbols for building a family tree.). In the information of the 1st degree relatives (parents, siblings, children) and relatives should contain statements on the state of health and to the presence of a genetic disorder or carrier status of both parents, 2nd degree (aunts, uncles, grandparents) also information on the ethnic and racial background and consanguineous marriages be included. consider are histories of previous pregnancies. If the suspicion of a genetic disorder is, relevant medical reports must be checked. Genetic screening tests are best carried out prior to conception. Traditionally, parents are offered, where there is a risk that they are asymptomatic carriers of a common Mendelian disease (see Table: Genetic screening for all ethnic groups). Diagnostic tests to specific abnormalities be offered to parents when it seems appropriate (see table: Indications for diagnostic genetic testing of the fetus). (N. D. Talk .: In Germany, the indications for genetic counseling of women and serve the discovery of fetal developmental disorders or abnormalities the methods [by the so-called maternity guidelines guidelines of the Federal Committee of Physicians and Health Insurers on medical care during the ) as the parent-ethnicity is controlled pregnancy and after childbirth, entered into force on 12 July 2003]. more complex and less well defined than previously thought, and because prenatal genetic tests are much cheaper and faster start some doctors, all potential (and becoming) parents, regardless of ethnicity, to screen (the so-called. Universal carrier screening). Consensus about which diseases should be tested, does not yet exist. Increasing the number of tests and reviews suggests that the complexity of the advice of pre-tests increased. Every pregnant woman should have a screening using multiple maternal serum markers (?-fetoprotein, ?-human chorionic gonadotropin [?-hCG], estriol, inhibin A; Noninvasive mother Screening: chromosomal disorders Serum screening of mother) should be able to neural tube defects, Down to recognize syndrome (and other chromosomal abnormalities) and some other birth defects. (N. D. Talk .: In Germany not part of the cash benefits, however, offered by some doctors as a so-called “individual health services” [IHS].) This screening is 15 to 20 weeks gestation (SSW) is performed. Diagnostic genetic testing of the fetus These studies are usually performed on chorionic villus sampling, amniocentesis or rarely percutaneous umbilical cord blood sample. You can set cover Mendelian anomalies all trisomies many other chromosomal abnormalities and several hundred. Submicroscopic chromosomal abnormalities are not detected by traditional karyotype tests and can only by microarray technologies such. As array comparative genomic hybridization identified. Usually tests are recommended at increased risk for fetal chromosomal abnormality (see table: Indications for diagnostic genetic testing of the fetus). Unlike the screening tests, the diagnostic fetal examinations are usually invasive and pose risks to the fetus. Therefore, these studies were not routinely women without risk factors recommended in the past. Since now, however, the fetal genetic diagnosis is generally available and security has been improved, fetal genetic testing all pregnant women, regardless of risk, recommended. The role of array comparative genomic hybridization in prenatal testing is under review; it is most commonly used to evaluate fetuses with structural anomalies. Preimplantation genetic diagnosis can for couples who take advantage of the in vitro fertilization, available (Methods: Preimplantation Genetic Diagnosis). Genetic screening for all ethnic groups Ethnicity disease Parental screening tests Prenatal diagnosis All Cystic Fibrosis DNA analysis of the 23 CFTR mutations that occur chorionic villus sampling (CVS) or amniocentesis to determine the genotype in ? 0.1% of the US population * Ashkenazi Jews † Canavan syndrome DNA analysis to detect the most common mutations CVS or amniocentesis for DNA analysis familial dysautonomia DNA analysis for the detection of the most common mutations CVS or amniocentesis for DNA analysis Tay-Sachs disease determination of serum-hexosaminidase A for evaluation of a defect; any DNA analysis CVS or amniocentesis for enzyme assay or molecular analysis for the determination of hexosaminidase A; DNA analysis people with dark skin color sickle cell anemia hemoglobin electrophoresis CVS or amniocentesis for genotyping (direct DNA analysis), cajun members Tay-Sachs disease determination of serum-hexosaminidase A for evaluation of a defect; any DNA analysis CVS or amniocentesis for enzyme assay or molecular analysis for the determination of hexosaminidase A Southeast Asian, Indian, African, people from the Mediterranean and Near East ?-thalassemia blood image; if MCV <80 fL Hemoglobin CVS or amniocentesis for determining the genotype (DNA or direct linkage analysis) Southeast Asian, Cambodians, Chinese, Filipinos, Lao, Vietnamese, ?-thalassemia blood image; if MCV <80 fL Hemoglobin CVS or amniocentesis to determine the genotype (DNA or direct linkage analysis) * A definitive diagnosis is not always possible; the sensitivity varies depending on the ethnic group. † For Ashkenazi Jews, some experts recommend a screening for Gaucher disease, Niemann-Pick disease type A, Fanconi anemia (syndrome) Group C, Bloom syndrome and mucolipidosis IV Most (90%) Jews are Ashkenazi. if a Jew does not know whether he is Ashkenazi, it should be investigated. CFTR = cystic fibrosis transmembrane conductance regulator; CVS = chorionic villus; MCV = mean corpuscular volume. Indications for diagnostic genetic testing of the fetus indication Note request for an investigation The investigation should be offered to all pregnant women regardless of risk. Maternal age at the expected birth of> 35 years The ACOG recommends that all pregnant women regardless of maternal age an invasive test to assess the fetal karyotype. Repeated previous habitual abortions A chromosomal analysis may be indicated for both parents. Chromosomal abnormality of an older child a chromosome analysis may be indicated for both parents. Paternal age> 50 years The need for research is controversial. Parental chromosomal disorder Not all parental chromosomal rearrangements are risks for the offspring. Suspected parental sex-linked Mendelian disease – If both parents diagnosed or suspected autosomal recessive Mendelian disease – Maternal serum marker levels *, which can take a trisomy 21 or 18 in the first trimester carrying out a chorionic villus sampling or amniocentesis in the second trimester Increased maternal ? (fetoprotein and doubtful ultrasound findings performing amniocentesis Structural changes in the fetus including increased nuchal transparency in the first trimester) in the ultrasound, the risk of fetal chromosomal abnormality depends on specific anatomical findings. * Measured in the first or second trimester. ACOG = American College of Obstetricians and Gynecologists. Methods With the exception of sonography are all methods for the diagnosis of genetic disease to invasive procedures with a slightly increased risk to the fetus. If severe abnormality was detected, the pregnancy can be terminated or treated the disease in some cases (eg. As fetal surgery to correct spina bifida). Even if none of these options is considered, some women want to before the birth of knowledge of fetal abnormalities. Sonography Some experts recommend routine sonography for all pregnant women. Other benefits to the ultrasound only for specific indications such as the check-up on suspicion of a genetic abnormality or pregnancy or as an aid to interpretation of abnormal maternal serum marker levels (n. D. Talk .: In Germany, part of prenatal care). If the ultrasound examination performed by experienced examiners, the sensitivity for major congenital malformations is high. However, some experimental conditions (eg. as oligohydramnios, maternal obesity, location of the fetus) impede optimal imaging. The ultrasound is noninvasive and involves far as is known, no risks for the pregnant woman or the fetus. A standard ultrasound is performed in the following situations: Confirm gestational age detection of fetal viability detecting a multiple pregnancy during the second or third trimester may identify severe malformations of intracranial structures, spine, heart, bladder, kidney, stomach, chest , the abdominal wall, the long bones and the umbilical cord Although ultrasonography provides only information on the structure, leave some structural abnormalities conclusions regarding genetic anomalies. Multiple anomalies may indicate a chromosomal disorder. Targeted sonography in high-resolution technique is performed in certain reference centers and provides more detailed images than standard sonography. For couples with a positive family history of congenital malformations (z. B. congenital heart disease, cleft lip and palate, pyloric stenosis), v. a. one that before birth (eg. B. posterior urethral valves with Mega bladder), or directly after birth (eg. as diaphragmatic hernia) can be treated successfully, this examination would be indicated. High-resolution sonography can be performed even with abnormal maternal serum marker levels. With the high-resolution sonography following faults can be detected: kidney malformations (. Eg renal [Potter syndrome], polycystic kidney disease) Lethal forms of skeletal dysplasia with shortened limbs (eg thanatophoric skeletal dysplasia, Achondrogenesis.) Intestinal malformations (eg obstruction. ) diaphragmatic microcephaly hydrocephalus is during the second trimester, the detection of structures that are statistically associated with an increased risk of fetal chromosomal abnormalities, for a more detailed risk assessment nützlich.Amniozentese in amniocentesis is transabdominal and ultrasonically guided a needle into the amniotic cavity introduced to amniotic fluid and to aspirate fetal cells for analysis, including the determination of chemical markers (z. B. ?-fetoprotein, acetylcholinesterase). The safest time for an amniocentesis is after the 14th week of pregnancy. Directly in front of amniocentesis sonography should be performed to assess the fetal heart activity and to determine gestational age, location of the placenta, amniotic fluid distribution and number of fetuses. If the mother is Rh-negative and not sensitized, it is given after the procedure 300 micrograms Rh0 (D) immunoglobulin to reduce the likelihood of sensitization (Fetal erythroblastosis: Prevention). Usually, amniocentesis pregnant women (d. Talk .: Note. In Germany controlled by the maternity guidelines) is offered> 35 years because they are at increased risk for a child with Down syndrome or another chromosomal abnormality. With the wide availability and improved safety of amniocentesis, the American College of Obstetricians and Gynecologists recommends that all pregnant women amniocentesis to determine the risk of fetal chromosomal disorders is offered. Occasionally, the amniotic fluid obtained is tinged with blood. Usually it is maternal blood, through the growth of the amnion is not affected; However, if it is fetal blood, it may erroneously increase in the amniotic fluid, the ?-fetoprotein levels. A dark red or brown liquid displays a previous history of intra-amniotic circulation and thus an increased risk of miscarriage. Green fruit water produced usually from a coloring by meconium, does not seem to increase the risk of miscarriage. Amniocentesis rarely leads to serious maternal illness (eg. As symptomatic amnionitis). With experienced investigators, the risk of miscarriage is 0.1 to 0.2%. Slight vaginal bleeding or heraussickerndes amniotic fluid are usually self-limiting and occur in 1-2% of the women studied. An amniocentesis before the 14th week of pregnancy, especially before the 13th SSW has a higher rate of miscarriage and an increased risk of a Pes equinovaru (clubfoot) for Folge.Chorionzottenbiopsie In chorionic villus sampling (chorionic villus sampling, CVS) are in chorionic villi aspirated a syringe and then cultured. The CVS provides the same information for fetal genetic and chromosomal status of the fetus as amniocentesis with similar accuracy. The CVS is however carried out between the 10th week of pregnancy and the end of the first trimester and makes the results available so earlier. Therefore, the pregnancy, if necessary, earlier (and thus safer and easier) to be terminated, or the parents can, if the results are normal, sooner relieved of their worries. Unlike the amniocentesis, CVS does not allow doctors to entmehmen amniotic fluid, and ?-fetoprotein can not be determined. Therefore, women in which a CVS was made a test for ?-fetoprotein in maternal serum in the 16.-18. SSW offered to assess the risk of fetal neural tube defects (non-invasive screening of the mother: serum screening mother to neural tube defects). Depending on the localization of the placenta (ultrasound determined) the CVS may be either via the insertion of a catheter through the cervix or via a needle which is inserted through the abdomen of the pregnant woman take place. After the CVS each Rh-negative, non-sensitized pregnant receives 300 ug Rh0 (D) immune globulin. Errors in diagnosis due to contamination by maternal cells are rare. Finding certain chromosomal abnormalities (eg. As a tetraploid) does not have to reflect the true chromosomal status of the fetus, but limited to the placental mosaicism. A limited to the placental mosaicism is detected in approximately 1% of CVS samples. Here it is advisable to consult a familiar with these anomalies experts. Occasionally another amniocentesis is necessary to obtain additional information. The rate of abortions, which have been triggered by a CVS, corresponds to that of amniocentesis (d. E. About 0.2%). Reduction defects of the extremities and the oro-akrale malformation complex of CVS have been attributed, but they are extremely rare when the CVS performed by an experienced examiner after the 10th week of pregnancy wird.Perkutane umbilical blood sampling Fetal blood samples can be obtained under ultrasound guidance by percutaneous puncture of the umbilical , The chromosome analysis can be customize within 48-72 hours. For this reason, a percutaneous umbilical blood sampling was (percutaneous umbilical blood sampling, PUBS) previously performed often when the result was needed quickly. This study was particularly useful in the late third trimester, especially if was raised at this time for the first time suspected fetal anomalies. Today, the genetic analysis of cells allows the amniotic fluid or chorionic villi by means of an interphase fluorescence in situ hybridization (FISH) a preliminary diagnosis (or exclusion) of frequent chromosome diseases within 24-48 hours; percutaneous umbilical blood sampling is rarely made in genetic indications. The rate of investigation related abortions is 1% .Genetische Präimplantationsdiagnostik A genetic diagnosis is possible in some cases even before the implantation, when in vitro fertilization is performed; to polar bodies of oocytes, blastomeres from embryos are used in the 6- to 8-cell stage or a Trophoblastprobe from the blastocyst. These studies are only in special centers available, are expensive and are primarily used for couples at high risk for certain simple inherited disorders (eg. As cystic fibrosis) or chromosomal abnormalities. Newer techniques are, however, reduce the costs and enable such studies on a larger scale. (. N. D Red .: preimplantation diagnosis is prohibited in Germany by the Embryo Protection Act. Polar Body Diagnosis, which is, however, reveal only the X-linked gene defects in the location, by the Embryo Protection Act possible and is carried out in Germany in some centers.) Preimplantation genetic diagnosis in embryos of older women the chance of success of pregnancy does not seem to increase. Non-invasive screening of mother Unlike invasive tests there is no risk of test-related complications in noninvasive maternal screening. After careful assessment of the risk of fetal abnormalities, noninvasive maternal screening women can assist in deciding whether an invasive test should be done. A noninvasive maternal screening for fetal chromosomal abnormalities should be offered to all pregnant women who have not yet chosen a amniocentesis or CVS. However, when a CVS is made, nor a maternal serum screening for the study of fetal neural tube defects should be offered. Normal values ??vary depending on the gestational age. Taking into account the maternal weight, diabetes mellitus, race and other factors corrections may be required in each case. A screening can in the first trimester, the second trimester or both times (referred to as sequential or integrated screening) are carried out. Each of the three options is acceptable. Maternal ?-fetoprotein levels should be measured in the second trimester to check whether neural tube defects are present. Tips and risks, measure the values ??of ?-fetoprotein in the mother in the second trimester to check for neural tube defects, regardless of other planned tests and the time of their execution. Screening in the first trimester sonography shows enlarged nuchal translucency in a fetus in the 10th week. (Figure by Jeffrey S. Dungan, MD) var model = {thumbnailUrl ‘/-/media/manual/professional/images/ultrasonography_nuchal_fetus_high_de.jpg?la=de&thn=0&mw=350’, imageUrl: ‘/ – / media / manual /professional/images/ultrasonography_nuchal_fetus_high_de.jpg?la=de&thn=0 ‘, title:’ the ultrasound shows enlarged nuchal translucency in a fetus in the 10th week ‘, description:’. u003Ca id = “v37897194 ” class = “”anchor “” u003e u003c / a u003e u003cdiv class = “”para “” u003e u003cp u003eDie chorionic villus sampling indicates that there is a fetus with down syndrome. u003c / p u003e u003c / div u003e ‘credits’ (Figure Jeffrey S. Dungan

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